2-芳基帕利酮是选择性抗锥虫药物。

2-Arylpaullones are selective antitrypanosomal agents.

机构信息

Technische Universität Braunschweig, Institut für Medizinische und Pharmazeutische Chemie, Beethovenstraße 55, D-38106 Braunschweig, Germany.

出版信息

Eur J Med Chem. 2013 Jun;64:396-400. doi: 10.1016/j.ejmech.2013.03.065. Epub 2013 Apr 10.

DOI:10.1016/j.ejmech.2013.03.065

PMID:23648975

Abstract

Antileishmanial paullone-chalcone hybrid molecules display antiparasitic activity against Trypanosoma brucei rhodesiense blood stream forms, albeit with low selectivity against human THP-1 cells. In order to develop less toxic analogues, paullones with acrylamide or aryl substituents in 2-position were synthesized, of which the latter exhibited potent antiparasitic activity with excellent selectivity profiles. The most potent compound identified in this study was 9-tert-butyl-2-(4-morpholinophenyl)paullone (3i) which inhibited the parasites at submicromolar concentrations (GI50 = 510 nM) with a selectivity index of 157.

摘要

抗利什曼原虫的保罗酮-查尔酮杂合体分子对布氏冈比亚锥虫血流形式表现出抗寄生虫活性，尽管对人 THP-1 细胞的选择性较低。为了开发毒性更低的类似物，合成了在 2-位具有丙烯酰胺或芳基取代基的保罗酮，其中后者表现出强大的抗寄生虫活性和优异的选择性特征。在这项研究中鉴定出的最有效化合物是 9-叔丁基-2-(4-吗啉基苯基)保罗酮（3i），它以亚微摩尔浓度（GI50 = 510 nM）抑制寄生虫，选择性指数为 157。